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    Clinical Trial Results:
    A 2-treatment period, randomized, placebo-controlled, multicenter parallel-group study to assess the safety of QAW039 when added to existing asthma therapy in GINA steps 3, 4 and 5 patients with uncontrolled asthma

    Summary
    EudraCT number
    		 2016-001560-11
    Trial protocol
    		 SK   DE   LV   EE   HU   BE   GR   AT   FR   CZ   LT   ES   NL   GB   PL   FI   BG   RO  
    Global end of trial date
    16 Mar 2020

    Results information
    Results version number
    		 v2(current)
    This version publication date
    20 Jun 2021
    First version publication date
    30 Sep 2020
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Correction to Adverse event reporting additional description section

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CQAW039A2315
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03052517
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    16 Mar 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    16 Mar 2020
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objectives for Treatment Period 1 (double-blind, 52-week treatment period) and Treatment Period 1 and Period 2 combined is: In patients with moderate-to-severe asthma receiving SoC asthma therapy, to evaluate the long-term safety of QAW039 (150 mg once daily and 450 mg once daily), compared with placebo, as assessed by:  treatment emergent adverse events (AEs);  treatment emergent serious adverse events (SAEs); and  study treatment discontinuations due to treatment emergent AEs.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Malaysia: 3
    Country: Number of subjects enrolled
    Mexico: 33
    Country: Number of subjects enrolled
    Netherlands: 10
    Country: Number of subjects enrolled
    Peru: 69
    Country: Number of subjects enrolled
    Philippines: 76
    Country: Number of subjects enrolled
    Poland: 64
    Country: Number of subjects enrolled
    Romania: 100
    Country: Number of subjects enrolled
    Russian Federation: 204
    Country: Number of subjects enrolled
    Saudi Arabia: 2
    Country: Number of subjects enrolled
    Serbia: 56
    Country: Number of subjects enrolled
    Singapore: 4
    Country: Number of subjects enrolled
    Slovakia: 116
    Country: Number of subjects enrolled
    Spain: 63
    Country: Number of subjects enrolled
    Switzerland: 3
    Country: Number of subjects enrolled
    Taiwan: 3
    Country: Number of subjects enrolled
    Argentina: 308
    Country: Number of subjects enrolled
    Australia: 9
    Country: Number of subjects enrolled
    Austria: 22
    Country: Number of subjects enrolled
    Belgium: 35
    Country: Number of subjects enrolled
    Brazil: 101
    Country: Number of subjects enrolled
    Bulgaria: 58
    Country: Number of subjects enrolled
    Canada: 51
    Country: Number of subjects enrolled
    China: 68
    Country: Number of subjects enrolled
    Colombia: 19
    Country: Number of subjects enrolled
    Czech Republic: 50
    Country: Number of subjects enrolled
    Estonia: 13
    Country: Number of subjects enrolled
    Finland: 3
    Country: Number of subjects enrolled
    France: 22
    Country: Number of subjects enrolled
    Germany: 53
    Country: Number of subjects enrolled
    Greece: 31
    Country: Number of subjects enrolled
    Guatemala: 65
    Country: Number of subjects enrolled
    Hungary: 127
    Country: Number of subjects enrolled
    India: 57
    Country: Number of subjects enrolled
    Israel: 32
    Country: Number of subjects enrolled
    Japan: 274
    Country: Number of subjects enrolled
    Latvia: 29
    Country: Number of subjects enrolled
    Lebanon: 20
    Country: Number of subjects enrolled
    Lithuania: 21
    Country: Number of subjects enrolled
    Turkey: 27
    Country: Number of subjects enrolled
    United Kingdom: 34
    Country: Number of subjects enrolled
    United States: 203
    Worldwide total number of subjects
    2538
    EEA total number of subjects
    851
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    118
    Adults (18-64 years)
    1972
    From 65 to 84 years
    448
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were from ARG, AUS, AUT, BEL, BRA, BGR, CAN, CHN, COL, CZE, EST, FIN, FRA, DEU, GRC, GTM, HUN, IND, ISR, JPN, LVA, LBN, LTU, MYS, MEX, NLD, PER, PHL, POL, ROU, RUS, SAU, SRB, SGP, SVK, ESP, CHE, TWN, TUR, GBR, USA

    Pre-assignment
    Screening details
    		 Eligible patients included patients completing a prior QAW039 Phase 3 study (CQAW039A2307, QAW039A2314, CQAW039A2316, or CQAW039A2317) and patients who had not previously participated in a QAW039 study.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 QAW039 150mg
    Arm description
    		 QAW039 150mg once daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    QAW039 150mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    QAW039 150mg once daily oral tablet

    Arm title
    		 QAW039 450 mg
    Arm description
    		 QAW039 450mg once daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    QAW039 450 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    QAW039 450 mg once daily oral tablet

    Arm title
    		 Placebo
    Arm description
    		 Placebo once daily
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo to QAW039
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo to QAW039 once daily oral tablet

    Number of subjects in period 1
    		QAW039 150mg QAW039 450 mg Placebo
    Started
    1093
    1085
    360
    Completed
    76
    71
    32
    Not completed
    1017
    1014
    328
         Adverse event, serious fatal
    3
    -
    1
         Physician decision
    4
    5
    1
         Study Terminated By Sponsor
    928
    938
    296
         Adverse event, non-fatal
    6
    5
    -
         Technical Problems
    -
    1
    -
         Pregnancy
    1
    -
    1
         Non-Compliance With Study Treatment
    -
    2
    -
         Subject/Guardian Decision
    50
    45
    22
         Lost to follow-up
    2
    4
    -
         Lack of efficacy
    23
    14
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    QAW039 150mg
    Reporting group description
    		 QAW039 150mg once daily

    Reporting group title
    QAW039 450 mg
    Reporting group description
    		 QAW039 450mg once daily

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo once daily

    Reporting group values
    		 QAW039 150mg QAW039 450 mg Placebo Total
    Number of subjects
    		 1093 1085 360 2538
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0
        Adolescents (12-17 years)
    		 48 53 17 118
        Adults (18-64 years)
    		 856 836 280 1972
        From 65-84 years
    		 189 196 63 448
        85 years and over
    		 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 50.1 ± 14.95 50.1 ± 15.55 49.9 ± 14.99 -
    Sex: Female, Male
    Units: Participants
        Female
    		 659 667 229 1555
        Male
    		 434 418 131 983
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    		 758 757 242 1757
        Black
    		 30 14 11 55
        Asian
    		 219 215 73 507
        Native American
    		 27 40 12 79
        Pacific Islander
    		 0 1 0 1
        Unknown
    		 0 9 2 11
        Other
    		 59 49 20 128

    End points

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    End points reporting groups
    Reporting group title
    QAW039 150mg
    Reporting group description
    		 QAW039 150mg once daily

    Reporting group title
    QAW039 450 mg
    Reporting group description
    		 QAW039 450mg once daily

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo once daily

    Subject analysis set title
    QAW039 150mg SAF
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    One patient received placebo. This patient was not included in QAW039 150 mg group in the SAF

    Subject analysis set title
    QAW039 450mg SAF
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    One patient had no treatment administered and thus was excluded from the SAF

    Subject analysis set title
    Placebo SAF
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    One patient in QAW039 150 mg group received placebo and was included in the placebo group in the SAF

    Primary: Number of participants with treatment emergent adverse events (AEs) up to week 52 - Cox Regression Model

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    End point title
    		 Number of participants with treatment emergent adverse events (AEs) up to week 52 - Cox Regression Model
    End point description
    Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs. For this Outcome Measure, AE up to week 52 are reported.
    End point type
    Primary
    End point timeframe
    52 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
    675
    654
    237
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.74
         upper limit
    		 1
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.72
         upper limit
    		 0.97
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.09

    Primary: Number of participants with treatment emergent adverse events (AEs) up to week 156 - Cox Regression Model

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    End point title
    		 Number of participants with treatment emergent adverse events (AEs) up to week 156 - Cox Regression Model
    End point description
    Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs
    End point type
    Primary
    End point timeframe
    156 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
    709
    681
    243
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.76
         upper limit
    		 1.02
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.85
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 0.99
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.86
         upper limit
    		 1.08

    Primary: Number of participants with treatment emergent serious adverse events (SAEs) up to week 52 - Cox Regression Model

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    End point title
    		 Number of participants with treatment emergent serious adverse events (SAEs) up to week 52 - Cox Regression Model
    End point description
    Serious Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +30 days were classified as treatment emergent SAEs. For this Outcome Measure, AE up to week 52 are reported.
    End point type
    Primary
    End point timeframe
    52 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
    73
    53
    29
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.51
         upper limit
    		 1.22
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.61
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 0.97
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.14

    Primary: Number of participants with treatment emergent serious adverse events (SAEs) up to week 156 - Cox Regression Model

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    End point title
    		 Number of participants with treatment emergent serious adverse events (SAEs) up to week 156 - Cox Regression Model
    End point description
    Serious Adverse events starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +30 days were classified as treatment emergent SAEs.
    End point type
    Primary
    End point timeframe
    156 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
    86
    63
    33
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.54
         upper limit
    		 1.22
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 0.97
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 1.11

    Primary: Number of participants with treatment emergent AEs leading to discontinuation from study treatment up to week 52 - Cox Regression Model

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    End point title
    		 Number of participants with treatment emergent AEs leading to discontinuation from study treatment up to week 52 - Cox Regression Model
    End point description
    Adverse events leading to study treatment discontinuation starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs leading to study treatment discontinuation. For this Outcome Measure, AE up to week 52 are reported.
    End point type
    Primary
    End point timeframe
    52 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
    26
    33
    9
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.47
         upper limit
    		 2.23
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.59
         upper limit
    		 2.64
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 2.1

    Primary: Number of participants with treatment emergent AEs leading to discontinuation from study treatment up to week 156 - Cox Regression Model

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    End point title
    		 Number of participants with treatment emergent AEs leading to discontinuation from study treatment up to week 156 - Cox Regression Model
    End point description
    Adverse events leading to study treatment discontinuation starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE) were classified as treatment emergent AEs leading to study treatment discontinuation
    End point type
    Primary
    End point timeframe
    156 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
    30
    37
    9
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.56
         upper limit
    		 2.56
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.67
         upper limit
    		 2.95
    Statistical analysis title
    		 Cox Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.96

    Secondary: Number of patients with at least one treatment emergent AE by primary system organ class up to week 52

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    End point title
    		 Number of patients with at least one treatment emergent AE by primary system organ class up to week 52
    End point description
    The number of patients per patient year of follow-up having a treatment emergent adverse event, categorized by system organ class. Treatment emergent adverse events are defined as an AEs starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE)
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
        Number of patients with at least one AE
    675
    654
    237
        Blood and lymphatic system disorders
    21
    10
    5
        Cardiac disorders
    11
    26
    7
        Congenital, familial and genetic disorders
    1
    3
    0
        Ear and labyrinth disorders
    16
    9
    8
        Endocrine disorders
    2
    6
    0
        Eye disorders
    13
    11
    9
        Gastrointestinal disorders
    88
    86
    32
        General disorders & administration site conditions
    38
    33
    7
        Hepatobiliary disorders
    9
    17
    7
        Immune system disorders
    11
    10
    6
        Infections and infestations
    400
    374
    145
        Injury, poisoning and procedural complications
    67
    52
    23
        Investigations
    79
    85
    20
        Metabolism and nutrition disorders
    53
    50
    21
        Musculoskeletal and connective tissue disorders
    91
    84
    24
        Neoplasms benign, malignant and unspecified
    13
    9
    3
        Nervous system disorders
    67
    73
    29
        Product issues
    1
    0
    0
        Psychiatric disorders
    18
    15
    9
        Renal and urinary disorders
    33
    41
    8
        Reproductive system and breast disorders
    14
    9
    4
        Respiratory, thoracic and mediastinal disorders
    308
    304
    135
        Skin and subcutaneous tissue disorders
    38
    39
    13
        Social circumstances
    1
    1
    3
        Vascular disorders
    39
    33
    9
    Statistical analysis title
    		 Logistic Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.626
         upper limit
    		 1.047
    Statistical analysis title
    		 Logistic Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.622
         upper limit
    		 1.038
    Statistical analysis title
    		 Logistic Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.821
         upper limit
    		 1.2

    Secondary: Number of patients with at least one treatment emergent AE by primary system organ class up to week 156

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    End point title
    		 Number of patients with at least one treatment emergent AE by primary system organ class up to week 156
    End point description
    The number of patients per patient year of follow-up having a treatment emergent adverse event, categorized by system organ class. Treatment emergent adverse events are defined as an AEs starting on or after the day of the first intake of study drug in this study and until the day of last intake of study drug +7 days (30 days in the case of a serious AE)
    End point type
    Secondary
    End point timeframe
    156 weeks
    End point values
    		 QAW039 150mg QAW039 450 mg Placebo
    Number of subjects analysed
    1081
    1077
    359
    Units: Participants
        Number of patients with at least one AE
    710
    682
    243
        Blood and lymphatic system disorders
    23
    12
    5
        Cardiac disorders
    16
    34
    7
        Congenital, familial and genetic disorders
    1
    3
    1
        Ear and labyrinth disorders
    18
    13
    9
        Endocrine disorders
    5
    7
    0
        Eye disorders
    16
    14
    9
        Gastrointestinal disorders
    101
    96
    38
        General disorders & administration site conditions
    43
    34
    8
        Hepatobiliary disorders
    10
    21
    8
        Immune system disorders
    11
    11
    6
        Infections and infestations
    436
    415
    151
        Injury, poisoning and procedural complications
    80
    63
    28
        Investigations
    90
    102
    24
        Metabolism and nutrition disorders
    61
    60
    23
        Musculoskeletal and connective tissue disorders
    102
    92
    31
        Neoplasms benign, malignant and unspecified
    17
    11
    3
        Nervous system disorders
    83
    77
    32
        Pregnancy, puerperium and perinatal conditions
    1
    0
    0
        Product issues
    1
    0
    0
        Psychiatric disorders
    23
    18
    9
        Renal and urinary disorders
    36
    45
    10
        Reproductive system and breast disorders
    17
    10
    4
        Respiratory, thoracic and mediastinal disorders
    336
    341
    144
        Skin and subcutaneous tissue disorders
    45
    45
    15
        Social circumstances
    1
    1
    3
        Vascular disorders
    45
    40
    13
    Statistical analysis title
    		 Logistc Regression Model
    Comparison groups
    QAW039 150mg v Placebo
    Number of subjects included in analysis
    1440
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.667
         upper limit
    		 1.125
    Statistical analysis title
    		 Logistic Regression Model
    Comparison groups
    QAW039 450 mg v Placebo
    Number of subjects included in analysis
    1436
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.83
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.643
         upper limit
    		 1.082
    Statistical analysis title
    		 Logistic Regression Model
    Comparison groups
    QAW039 150mg v QAW039 450 mg
    Number of subjects included in analysis
    2158
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.96
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.794
         upper limit
    		 1.167

    Secondary: Number of treatment emergent patient deaths due to an asthma exacerbation up to week 52

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    End point title
    		 Number of treatment emergent patient deaths due to an asthma exacerbation up to week 52
    End point description
    The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    		 QAW039 150mg SAF QAW039 450mg SAF Placebo SAF
    Number of subjects analysed
    1092
    1084
    361
    Units: Number of deaths
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of treatment emergent patient deaths due to an asthma exacerbation up to week 156

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    End point title
    		 Number of treatment emergent patient deaths due to an asthma exacerbation up to week 156
    End point description
    The number of treatment emergent patient deaths due to an asthma exacerbation. Treatment emergent deaths are defined as deaths resulting from treatment emergent AEs.
    End point type
    Secondary
    End point timeframe
    156 weeks
    End point values
    		 QAW039 150mg SAF QAW039 450mg SAF Placebo SAF
    Number of subjects analysed
    1092
    1084
    361
    Units: Number of deaths
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Rate of treatment emergent severe asthma exacerbation episodes requiring hospitalizations per person year up to week 52

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    End point title
    		 Rate of treatment emergent severe asthma exacerbation episodes requiring hospitalizations per person year up to week 52
    End point description
    Number of treatment emergent severe asthma exacerbation episodes requiring hospitalizations (any visit to the hospital requiring an overnight stay or an emergency room visit greater than 24 hours) per person year of follow-up. Treatment emergent severe asthma exacerbation episodes are defined as episodes occurring on or after the day of the first intake of study drug and until the day of last intake of study drug +7 days (30 days in the case of a serious AE). Rate of exacerbations per person year = total number of exacerbations / total number of treatment years
    End point type
    Secondary
    End point timeframe
    52 weeks
    End point values
    		 QAW039 150mg SAF QAW039 450mg SAF Placebo SAF
    Number of subjects analysed
    1092
    1084
    361
    Units: Hospitalizations per person year
        number (not applicable)
    0.04
    0.02
    0.06
    No statistical analyses for this end point

    Secondary: Rate of treatment emergent severe asthma exacerbation episodes requiring hospitalizations per person year up to week 156

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    End point title
    		 Rate of treatment emergent severe asthma exacerbation episodes requiring hospitalizations per person year up to week 156
    End point description
    Number of treatment emergent severe asthma exacerbation episodes requiring hospitalizations (any visit to the hospital requiring an overnight stay or an emergency room visit greater than 24 hours) per person year of follow-up. Treatment emergent severe asthma exacerbation episodes are defined as episodes occurring on or after the day of the first intake of study drug and until the day of last intake of study drug +7 days (30 days in the case of a serious AE). Rate of exacerbations per person year = total number of exacerbations / total number of treatment years
    End point type
    Secondary
    End point timeframe
    156 weeks
    End point values
    		 QAW039 150mg SAF QAW039 450mg SAF Placebo SAF
    Number of subjects analysed
    1092
    1084
    361
    Units: Hospitalizations per person year
        number (not applicable)
    0.04
    0.02
    0.05
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from first dose of study treatment until end of study treatment plus 7 days post treatment (30 days in the case of a serious AE), up to maximum duration of 156 weeks.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    QAW039 450 mg
    Reporting group description
    		 QAW039 450 mg

    Reporting group title
    QAW039 150 mg
    Reporting group description
    		 QAW039 150 mg

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo

    Serious adverse events
    		 QAW039 450 mg QAW039 150 mg Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    64 / 1084 (5.90%)
    87 / 1092 (7.97%)
    33 / 361 (9.14%)
         number of deaths (all causes)
    1
    3
    1
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    0 / 1084 (0.00%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cervix carcinoma
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric cancer
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intraductal proliferative breast lesion
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myeloproliferative neoplasm
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal neoplasm
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal cancer
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tongue neoplasm malignant stage unspecified
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Transitional cell carcinoma
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Aortic stenosis
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Pregnancy
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Death
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Fatigue
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperplasia
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Swelling face
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Eosinophilic granulomatosis with polyangiitis
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Endometrial hyperplasia
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aphonia
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    16 / 1084 (1.48%)
    30 / 1092 (2.75%)
    13 / 361 (3.60%)
         occurrences causally related to treatment / all
    2 / 21
    2 / 44
    2 / 20
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diaphragmatic paralysis
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 1084 (0.18%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pulmonary mass
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wheezing
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 1084 (0.09%)
    3 / 1092 (0.27%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Electrocardiogram Q wave abnormal
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram T wave inversion
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Oxygen saturation decreased
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Exposure to allergen
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Femur fracture
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture displacement
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Joint injury
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar vertebral fracture
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rib fracture
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skeletal injury
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Wrist fracture
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Fibrous dysplasia of bone
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skeletal dysplasia
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 1084 (0.09%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arteriosclerosis coronary artery
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    2 / 1084 (0.18%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular extrasystoles
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain stem haemorrhage
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebral ischaemia
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    2 / 1084 (0.18%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colloid brain cyst
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Dyspraxia
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Facial paralysis
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Guillain-Barre syndrome
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    0 / 1084 (0.00%)
    3 / 1092 (0.27%)
    2 / 361 (0.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar radiculopathy
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood loss anaemia
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Meniere's disease
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tympanic membrane perforation
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vertigo
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal hernia
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haemorrhoids
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    2 / 361 (0.55%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritoneal cyst
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritoneal haemorrhage
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Strangulated umbilical hernia
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    2 / 1084 (0.18%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 1084 (0.09%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Calculus urinary
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic kidney disease
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    2 / 1084 (0.18%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 1084 (0.00%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc degeneration
         subjects affected / exposed
    0 / 1084 (0.00%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 1084 (0.00%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    3 / 1084 (0.28%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis bacterial
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue haemorrhagic fever
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 1084 (0.09%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lung abscess
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    4 / 1084 (0.37%)
    7 / 1092 (0.64%)
    2 / 361 (0.55%)
         occurrences causally related to treatment / all
    0 / 4
    2 / 7
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 1084 (0.00%)
    2 / 1092 (0.18%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Rhinitis
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 1084 (0.00%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 1084 (0.00%)
    2 / 1092 (0.18%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tuberculosis
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 1084 (0.00%)
    0 / 1092 (0.00%)
    1 / 361 (0.28%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vaginal abscess
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Diabetes mellitus inadequate control
         subjects affected / exposed
    0 / 1084 (0.00%)
    1 / 1092 (0.09%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperlipidaemia
         subjects affected / exposed
    1 / 1084 (0.09%)
    0 / 1092 (0.00%)
    0 / 361 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 QAW039 450 mg QAW039 150 mg Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    499 / 1084 (46.03%)
    525 / 1092 (48.08%)
    190 / 361 (52.63%)
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    42 / 1084 (3.87%)
    30 / 1092 (2.75%)
    2 / 361 (0.55%)
         occurrences all number
    48
    32
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    30 / 1084 (2.77%)
    30 / 1092 (2.75%)
    11 / 361 (3.05%)
         occurrences all number
    34
    33
    11
    Nervous system disorders
    Headache
         subjects affected / exposed
    29 / 1084 (2.68%)
    41 / 1092 (3.75%)
    24 / 361 (6.65%)
         occurrences all number
    40
    63
    30
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    275 / 1084 (25.37%)
    291 / 1092 (26.65%)
    125 / 361 (34.63%)
         occurrences all number
    485
    523
    270
    Rhinitis allergic
         subjects affected / exposed
    28 / 1084 (2.58%)
    19 / 1092 (1.74%)
    11 / 361 (3.05%)
         occurrences all number
    29
    22
    16
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    11 / 1084 (1.01%)
    22 / 1092 (2.01%)
    8 / 361 (2.22%)
         occurrences all number
    11
    25
    8
    Back pain
         subjects affected / exposed
    31 / 1084 (2.86%)
    29 / 1092 (2.66%)
    10 / 361 (2.77%)
         occurrences all number
    36
    32
    11
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    55 / 1084 (5.07%)
    75 / 1092 (6.87%)
    38 / 361 (10.53%)
         occurrences all number
    69
    89
    54
    Influenza
         subjects affected / exposed
    28 / 1084 (2.58%)
    30 / 1092 (2.75%)
    9 / 361 (2.49%)
         occurrences all number
    28
    32
    11
    Nasopharyngitis
         subjects affected / exposed
    106 / 1084 (9.78%)
    110 / 1092 (10.07%)
    36 / 361 (9.97%)
         occurrences all number
    146
    154
    51
    Pharyngitis
         subjects affected / exposed
    22 / 1084 (2.03%)
    34 / 1092 (3.11%)
    15 / 361 (4.16%)
         occurrences all number
    27
    35
    17
    Sinusitis
         subjects affected / exposed
    28 / 1084 (2.58%)
    39 / 1092 (3.57%)
    9 / 361 (2.49%)
         occurrences all number
    35
    43
    9
    Upper respiratory tract infection
         subjects affected / exposed
    43 / 1084 (3.97%)
    72 / 1092 (6.59%)
    25 / 361 (6.93%)
         occurrences all number
    56
    83
    33
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    31 / 1084 (2.86%)
    14 / 1092 (1.28%)
    12 / 361 (3.32%)
         occurrences all number
    33
    15
    14
    Urinary tract infection
         subjects affected / exposed
    37 / 1084 (3.41%)
    23 / 1092 (2.11%)
    11 / 361 (3.05%)
         occurrences all number
    46
    25
    11
    Viral upper respiratory tract infection
         subjects affected / exposed
    31 / 1084 (2.86%)
    34 / 1092 (3.11%)
    9 / 361 (2.49%)
         occurrences all number
    37
    40
    12

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Jan 2018
    The key change to the protocol related to the removal of references and discussions regarding the Oral Corticosteroid Tapering Study (QAW039A2319), a Phase 3 study that was cancelled for strategic reasons before being initiated. The sample size for Study A2315 was also increased to account for the number of planned patients from the cancelled Oral Corticosteroid Tapering study. This amendment was not considered to have affected the interpretation of study results, as the changes were minor and occurred prior to study unblinding.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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